Omics Technologies in Evaluating New Insights into Molecular Aspects of Human Health

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Integrative Metabolomics".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 14936

Special Issue Editors

Department of Pharmacy, University of G. d'Annunzio Chieti-Pescara, Chieti, Italy
Interests: proteomics; metabolomics; mass spectrometry; extracellular vesicles; neurological diseases
Special Issues, Collections and Topics in MDPI journals
Department of Medial, Oral and Biotechnological Science, University of G. d'Annunzio of Chieti-Pescara, Chieti, Italy
Interests: proteomics; metabolomics; biomarker discovery; multiple sclerosis; extracellular vesicles
Special Issues, Collections and Topics in MDPI journals
Department of Innovative Technologies in Medicine and Dentistry, Medicine and Aging Science, Analytical Biochemistry and Proteomics Unit, Center for Advanced Studies and Technology (CAST),“G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
Interests: proteomics; metabolomics; LC-MS/MS; bioanalytical mass spectrometry; lipidomics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Emerging multi-omics strategies are becoming a powerful tool to gain deep insights into biological systems. In this scenario, understanding biochemical modifications will require the application of innovative qualitative and quantitative approaches, and their integration with novel interdisciplinary combined methods. Moreover, the molecular bases of diseases are often poorly understood, since they depend on multifactorial events like aging, gender, diet, pharmacological intervention, etc.

This Special Issue aims to collect papers recounting recent innovative high-throughput approaches (omics), such as genomics, transcriptomics, proteomics, and metabolomics, as well as bioinformatics and other related topics, in order to provide new insights into the molecular aspects of pathophysiology and biochemistry of human health.

We invite authors to contribute original research articles, method papers, as well as review articles that will address methodological development and/or new biological knowledge at molecular level through omics strategies. Potential topics include, but are not limited to, the following: molecular characterization of normal and diseased tissues/cells/biofluids; omics approaches and biomarker discovery; novel methods for the detection and analysis of metabolites/proteins; bioinformatics for the integration of omics data.

Prof. Piero Del Boccio
Prof. Damiana Pieragostino
Dr. Ilaria Cicalini
Guest Editors

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Keywords

  • Metabolomics
  • Lipidomics
  • Proteomics
  • Bioinformatics
  • Disease Biomarkers
  • Mass Spectrometry
  • Biochemical Pathways

Published Papers (6 papers)

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Research

10 pages, 734 KiB  
Article
Identification of Serum Oxylipins Associated with the Development of Coronary Artery Disease: A Nested Case-Control Study
by Kuang-Mao Chiang, Jia-Fu Chen, Chin-An Yang, Lili Xiu, Hsin-Chou Yang, Lie-Fen Shyur and Wen-Harn Pan
Metabolites 2022, 12(6), 495; https://doi.org/10.3390/metabo12060495 - 30 May 2022
Viewed by 1458
Abstract
Coronary artery disease (CAD) is among the leading causes of death globally. The American Heart Association recommends that people should consume more PUFA-rich plant foods to replace SFA-rich ones to lower serum cholesterol and prevent CAD. However, PUFA may be susceptible to oxidation [...] Read more.
Coronary artery disease (CAD) is among the leading causes of death globally. The American Heart Association recommends that people should consume more PUFA-rich plant foods to replace SFA-rich ones to lower serum cholesterol and prevent CAD. However, PUFA may be susceptible to oxidation and generate oxidized products such as oxylipins. In this study, we investigated whether the blood oxylipin profile is associated with the risk of developing CAD and whether including identified oxylipins may improve the predictability of CAD risk. We designed a nested case-control study with 77 cases and 148 matched controls from a 10-year follow-up of the Nutrition and Health Survey in a Taiwanese cohort of 720 people aged 50 to 70. A panel of 46 oxylipins was measured for baseline serum samples. We discovered four oxylipins associated with CAD risk. 13-oxo-ODE, which has been previously found in formed plagues, was positively associated with CAD (OR = 5.02, 95%CI = 0.85 to 15.6). PGE2/PGD2, previously shown to increase cardiac output, was inversely associated (OR = 0.16, 95%CI = 0.06 to 0.42). 15-deoxy-PGJ2, with anti-inflammatory and anti-apoptosis effects on cardiomyocytes (OR = 0.26, 95%CI = 0.09 to 0.76), and 5-HETE, which was associated with inflammation (OR = 0.28, 95%CI = 0.10 to 0.78), were also negatively associated as protective factors. Adding these four oxylipins to the traditional risk prediction model significantly improved CAD prediction. Full article
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16 pages, 3038 KiB  
Article
Circulating Metabolites as Biomarkers of Disease in Patients with Mesial Temporal Lobe Epilepsy
by Alexandre B. Godoi, Amanda M. do Canto, Amanda Donatti, Douglas C. Rosa, Danielle C. F. Bruno, Marina K. Alvim, Clarissa L. Yasuda, Lucas G. Martins, Melissa Quintero, Ljubica Tasic, Fernando Cendes and Iscia Lopes-Cendes
Metabolites 2022, 12(5), 446; https://doi.org/10.3390/metabo12050446 - 17 May 2022
Cited by 1 | Viewed by 2731
Abstract
A major challenge in the clinical management of patients with mesial temporal lobe epilepsy (MTLE) is identifying those who do not respond to antiseizure medication (ASM), allowing for the timely pursuit of alternative treatments such as epilepsy surgery. Here, we investigated changes in [...] Read more.
A major challenge in the clinical management of patients with mesial temporal lobe epilepsy (MTLE) is identifying those who do not respond to antiseizure medication (ASM), allowing for the timely pursuit of alternative treatments such as epilepsy surgery. Here, we investigated changes in plasma metabolites as biomarkers of disease in patients with MTLE. Furthermore, we used the metabolomics data to gain insights into the mechanisms underlying MTLE and response to ASM. We performed an untargeted metabolomic method using magnetic resonance spectroscopy and multi- and univariate statistical analyses to compare data obtained from plasma samples of 28 patients with MTLE compared to 28 controls. The patients were further divided according to response to ASM for a supplementary and preliminary comparison: 20 patients were refractory to treatment, and eight were responsive to ASM. We only included patients using carbamazepine in combination with clobazam. We analyzed the group of patients and controls and found that the profiles of glucose (p = 0.01), saturated lipids (p = 0.0002), isoleucine (p = 0.0001), β-hydroxybutyrate (p = 0.0003), and proline (p = 0.02) were different in patients compared to controls (p < 0.05). In addition, we found some suggestive metabolites (without enough predictability) by multivariate analysis (VIP scores > 2), such as lipoproteins, lactate, glucose, unsaturated lipids, isoleucine, and proline, that might be relevant to the process of pharmacoresistance in the comparison between patients with refractory and responsive MTLE. The identified metabolites for the comparison between MTLE patients and controls were linked to different biological pathways related to cell-energy metabolism and pathways related to inflammatory processes and the modulation of neurotransmitter release and activity in MTLE. In conclusion, in addition to insights into the mechanisms underlying MTLE, our results suggest that plasma metabolites may be used as disease biomarkers. These findings warrant further studies exploring the clinical use of metabolites to assist in decision-making when treating patients with MTLE. Full article
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13 pages, 1769 KiB  
Article
Metabolomics and Inflammatory Mediator Profiling for the Differentiation of Life-Threatening and Non-Severe Appendicitis in the Pediatric Population
by Nusrat S. Shommu, Jaime Blackwood, Craig N. Jenne, Ari R. Joffe, Dori-Ann Martin, Beata Mickiewicz, Mary Brindle, Robin Eccles, Hans J. Vogel, Graham C. Thompson and on behalf of the Alberta Sepsis Network
Metabolites 2021, 11(10), 664; https://doi.org/10.3390/metabo11100664 - 28 Sep 2021
Cited by 1 | Viewed by 1739
Abstract
While children with appendicitis often have excellent clinical outcomes, some develop life-threatening complications including sepsis and organ dysfunction requiring pediatric intensive care unit (PICU) support. Our study applied a metabolomics and inflammatory protein mediator (IPM) profiling approach to determine the bio-profiles of children [...] Read more.
While children with appendicitis often have excellent clinical outcomes, some develop life-threatening complications including sepsis and organ dysfunction requiring pediatric intensive care unit (PICU) support. Our study applied a metabolomics and inflammatory protein mediator (IPM) profiling approach to determine the bio-profiles of children who developed severe appendicitis compared with those that did not. We performed a prospective case-control study of children aged 0–17 years with a diagnosis of appendicitis. Cases had severe disease resulting in PICU admission. Primary controls had moderate appendicitis (perforation without PICU); secondary controls had mild appendicitis (non-perforated). Serum samples were analyzed using Proton Nuclear Magnetic Resonance (1H NMR) Spectroscopy and Gas Chromatography-Mass Spectrometry (GC-MS); IPM analysis was performed using plasma bead-based multiplex profiling. Comparisons were made using multivariate data statistical analysis. Fifty-three children were included (15 severe, 38 non-severe). Separation between severe and moderate appendicitis demonstrated excellent sensitivity and specificity (100%, 88%; 14 compounds), separation between severe and mild appendicitis also showed excellent sensitivity and specificity (91%, 90%; 16 compounds). Biomarker patterns derived from metabolomics and IPM profiling are capable of distinguishing children with severe appendicitis from those with less severe disease. These findings provide an important first step towards developing non-invasive diagnostic tools for clinicians in early identification of children who are at a high risk of developing severe appendicitis. Full article
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16 pages, 1290 KiB  
Article
Differential Glycosylation Levels in Saliva from Patients with Lung or Breast Cancer: A Preliminary Assessment for Early Diagnostic Purposes
by Andrea Ragusa, Pietrina Romano, Marcello Salvatore Lenucci, Emanuela Civino, Daniele Vergara, Elena Pitotti, Cosimo Neglia, Alessandro Distante, Giampiero Diego Romano, Nicola Di Renzo, Giammarco Surico, Prisco Piscitelli and Michele Maffia
Metabolites 2021, 11(9), 566; https://doi.org/10.3390/metabo11090566 - 24 Aug 2021
Cited by 7 | Viewed by 2901
Abstract
Glycans play a fundamental role in several biological processes, such as cell–cell adhesion, signaling, and recognition. Similarly, abnormal glycosylation is involved in many pathological processes, among which include tumor growth and progression. Several highly glycosylated proteins found in blood are currently used in [...] Read more.
Glycans play a fundamental role in several biological processes, such as cell–cell adhesion, signaling, and recognition. Similarly, abnormal glycosylation is involved in many pathological processes, among which include tumor growth and progression. Several highly glycosylated proteins found in blood are currently used in clinical practice as cancer biomarkers (e.g., CA125, PSA, and CA19-9). The development of novel non-invasive diagnostic procedures would greatly simplify the screening and discovery of pathologies at an early stage, thus also allowing for simpler treatment and a higher success rate. In this observational study carried out on 68 subjects diagnosed with either breast or lung cancer and 34 healthy volunteers, we hydrolyzed the glycoproteins in saliva and quantified the obtained free sugars (fucose, mannose, galactose, glucosamine, and galactosamine) by using high-performance anion-exchange chromatography with pulsed-amperometric detection (HPAEC-PAD). The glycosidic profiles were compared by using multivariate statistical analysis, showing differential glycosylation patterns among the three categories. Furthermore, Receiver Operating Characteristics (ROC) analysis allowed obtaining a reliable and minimally invasive protocol able to discriminate between healthy and pathological subjects. Full article
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16 pages, 2447 KiB  
Article
Analytical Evaluation of the Ideal Strategy for High-Throughput Flow Injection Analysis by Tandem Mass Spectrometry in Routine Newborn Screening
by Ilaria Cicalini, Silvia Valentinuzzi, Damiana Pieragostino, Ada Consalvo, Mirco Zucchelli, Simone Donzelli, Davide Ambrogi, Heather A. Brown, Lisa J. Calton, Liborio Stuppia, Vincenzo De Laurenzi, Piero Del Boccio and Claudia Rossi
Metabolites 2021, 11(8), 473; https://doi.org/10.3390/metabo11080473 - 22 Jul 2021
Cited by 7 | Viewed by 2203
Abstract
The introduction of tandem mass spectrometry (MS/MS) to clinical laboratories and the advent of expanded newborn screening (NBS) were crucial changes to public health programs worldwide. Speed, robustness, accuracy, selectivity, and specificity of analysis are all requirements of expanded NBS and are needed [...] Read more.
The introduction of tandem mass spectrometry (MS/MS) to clinical laboratories and the advent of expanded newborn screening (NBS) were crucial changes to public health programs worldwide. Speed, robustness, accuracy, selectivity, and specificity of analysis are all requirements of expanded NBS and are needed to minimize false positive results risks, to possibly eliminate false negatives, and to improve the positive predictive value of NBS. In this study, we firstly evaluated the analytical performances of the RenataDX Screening System, a fully integrated flow-injection MS/MS (FIA-MS/MS) IVD system for high-throughput dried blood spot (DBS) analysis in a routine NBS laboratory. Since a choice of several commercial NBS kits is available, we sought to compare NeoBaseTM 2 (PerkinElmer®) and MassChrom® (Chromsystems) non-derivatized kits on the RenataDX platform by evaluating their analytical performances. Moreover, we verified the degree of correlation between data obtained by the two different NBS MS/MS kits by FIA-MS/MS of over 500 samples. Our data suggest that both methods correlate well with clinically insignificant differences that do not impact the NBS result. Finally, while NeoBase™ 2 offers an easier and faster sample preparation, MassChrom® provides a cleaner sample extract which empirically should improve instrument reliability. Full article
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14 pages, 2078 KiB  
Article
Profiling of Cerebrospinal Fluid Lipids and Their Relationship with Plasma Lipids in Healthy Humans
by Kosuke Saito, Kotaro Hattori, Shinsuke Hidese, Daimei Sasayama, Tomoko Miyakawa, Ryo Matsumura, Megumi Tatsumi, Yuuki Yokota, Miho Ota, Hiroaki Hori and Hiroshi Kunugi
Metabolites 2021, 11(5), 268; https://doi.org/10.3390/metabo11050268 - 24 Apr 2021
Cited by 11 | Viewed by 2462
Abstract
Lipidomics provides an overview of lipid profiles in biological systems. Although blood is commonly used for lipid profiling, cerebrospinal fluid (CSF) is more suitable for exploring lipid homeostasis in brain diseases. However, whether an individual’s background affects the CSF lipid profile remains unclear, [...] Read more.
Lipidomics provides an overview of lipid profiles in biological systems. Although blood is commonly used for lipid profiling, cerebrospinal fluid (CSF) is more suitable for exploring lipid homeostasis in brain diseases. However, whether an individual’s background affects the CSF lipid profile remains unclear, and the association between CSF and plasma lipid profiles in heathy individuals has not yet been defined. Herein, lipidomics approaches were employed to analyze CSF and plasma samples obtained from 114 healthy Japanese subjects. Results showed that the global lipid profiles differed significantly between CSF and plasma, with only 13 of 114 lipids found to be significantly correlated between the two matrices. Additionally, the CSF total protein content was the primary factor associated with CSF lipids. In the CSF, the levels of major lipids, namely, phosphatidylcholines, sphingomyelins, and cholesterolesters, correlated with CSF total protein levels. These findings indicate that CSF lipidomics can be applied to explore changes in lipid homeostasis in patients with brain diseases. Full article
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